Aldehydes dehydration

Crossed aldol condensation of an anion generated a- to a ketone equivalent with o, /3-unsaturated aldehyde, dehydration and release of the ketone is an effective way of generation of dienones. Corey and Enders found that a-lithiated /V,/V-dirnethylhydrazones undergo 1,2-addition to the aldehydes and ketones to form /1-hydroxy derivatives. Sequential treatment of the intermediate with sodium periodate and methanesulphonyl chloride-triethylamine furnishes , -2,4-dienone derivative (equation 57)94. 

Perkin 1 Anhydride — CH—COOCOR Aromatic aldehyde Dehydration usually follows... 

The first step is a condensation of the aldol type (see Section 5.18.2, p. 799) involving the nucleophilic addition of the carbanion derived from the methyl ketone to the carbonyl-carbon of the aromatic aldehyde. Dehydration of the hydroxyketone to form the conjugated unsaturated carbonyl compound occurs spontaneously. 

In an aliphatic system. Stork has reported the regioselective lithiation of chelating enamines such as (9), to give vinyl carbanions such as (10 Scheme 6). Woik-up often results in hydrolysis of the enamine, and in die case of addition to aldehydes, dehydration. ... 

Carboxylic acids show strongly exothermic reactions with HsO" " and should therefore react at the collisional limit. As with alcohols and aldehydes, dehydration reactions have been identified for all but the smallest acids, formic and acetic [38]. However, for the small number of carboxylic acids whose reactions have been characterized, the non-dissociative channel dominates (>90%) in almost every case. Dehydration is also an issue for esters, although non-dissociative proton transfer has been established as the dominant reaction channel for many relatively simple esters [38], The formates, methyl and ethyl formate, are somewhat unusual in that their dissociative channels, both accounting for <5% of product yield at 300 K, involve CO ejection rather than dehydration. With esters derived from propyl alcohol and higher alcohols, fragmentation is ubiquitous and can involve a number of reaction channels [39]. 

Reformatski reaction Aldehydes and ketones react with a-bromo- fatty acid esters in the presence of zinc powder to give -hydroxy-esters which may be dehydrated to give a-, 0-unsaturated esters. a-Chloroesters will react if copper powder is used in conjunction with the zinc. 

Molisch s Test. Dissolve about 01 g. of the carbohydrate in z ml. of water (for starch use 2 ml. of starch solution ), add 2-3 drops of a 1 % alcoholic solution of i-naphthol (ignoring traces of the latter precipitated by the water) and then carefully pour 2 ml. of cone. H2SO4 down the side of the test-tube so that it forms a heavy layer at the bottom. A deep violet coloration is produced where the liquids meet. This coloration is due apparently to the formation of an unstable condensation product of i-naphthol with furfural (an aldehyde produced by the dehydration of the carbohydrate). 

Metallic sodium. This metal is employed for the drying of ethers and of saturated and aromatic hydrocarbons. The bulk of the water should first be removed from the liquid or solution by a preliminary drying with anhydrous calcium chloride or magnesium sulphate. Sodium is most effective in the form of fine wire, which is forced directly into the liquid by means of a sodium press (see under Ether, Section II,47,i) a large surface is thus presented to the liquid. It cannot be used for any compound with which it reacts or which is affected by alkalis or is easily subject to reduction (due to the hydrogen evolved during the dehydration), viz., alcohols, acids, esters, organic halides, ketones, aldehydes, and some amines. 

Both o-aminobenzyl aldehydes and ketones rapidly cyclize and undergo dehydration to indoles. The generation of these carbonyl compounds therefore represents a quite reliable route to indoles. The complication is that while there... 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Secondary amines are compounds of the type R2NH They add to aldehydes and ketones to form carbmolammes but their carbmolamme intermediates can dehydrate to a stable product only m the direction that leads to a carbon-carbon double bond... 

The p hydroxy aldehyde products of aldol addition undergo dehydration on heat mg to yield a f3 unsaturated aldehydes... 

Conjugation of the newly formed double bond with the carbonyl group stabilizes the a p unsaturated aldehyde provides the driving force for the dehydration and controls Its regioselectivity Dehydration can be effected by heating the aldol with acid or base Normally if the a p unsaturated aldehyde is the desired product all that is done is to carry out the base catalyzed aldol addition reaction at elevated temperature Under these conditions once the aldol addition product is formed it rapidly loses water to form the a p unsaturated aldehyde... 

A reaction of great synthetic val ue for carbon-carbon bond for mation Nucleophilic addition of an enolate ion to a carbonyl group followed by dehydration of the 3 hydroxy aldehyde yields an a p unsaturated aldehyde... 

Section 20 18 Nitnles are prepared by nucleophilic substitution (8 2) of alkyl halides with cyanide ion by converting aldehydes or ketones to cyanohydrins (Table 20 6) or by dehydration of amides... 

Primary amines undergo nucleo philic addition to the carbonyl group of aldehydes and ketones to form carbinol amines These carbinolamines dehydrate under the conditions of their formation to give N substituted imines Secondary amines yield enamines... 

Aldol condensation (Sections 18 9-18 10) When an aldol ad dition IS carried out so that the 3 hydroxy aldehyde or ke tone dehydrates under the conditions of its formation the product IS described as ansing by an aldol condensation... 

Reactions with Aldehydes and Ketones. The base-catalyzed self-addition of acetaldehyde leads to formation of the dimer, acetaldol [107-89-1/, which can be hydrogenated to form 1,3-butanediol [107-88-0] or dehydrated to form crotonaldehyde [4170-30-3]. Crotonaldehyde can also be made directiy by the vapor-phase condensation of acetaldehyde over a catalyst (53). 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

Polymeric OC-Oxygen-Substituted Peroxides. Polymeric peroxides (3) are formed from the following reactions ketone and aldehydes with hydrogen peroxide, ozonization of unsaturated compounds, and dehydration of a-hydroxyalkyl hydroperoxides consequendy, a variety of polymeric peroxides of this type exist. Polymeric peroxides are generally viscous Hquids or amorphous soHds, are difficult to characterize, and are prone to explosive decomp o sition. 

Dijbner-von Miller Synthesis. A much less violent synthetic pathway, the Dn bner-von Miller, uses hydrochloric acid or 2inc chloride as the catalyst (43). As in the modified Skraup, a,P-unsaturated aldehydes and ketones make the dehydration of glycerol uimecessary, and allow a wider variety of substitution patterns. No added oxidant is required. With excess aniline the reaction proceeds as follows ... 

Hoffmaim-La Roche has produced -carotene since the 1950s and has rehed on core knowledge of vitamin A chemistry for the synthesis of this target. In this approach, a five-carbon homologation of vitamin A aldehyde (19) is accompHshed by successive acetalizations and enol ether condensations to prepare the aldehyde (46). Metal acetyUde coupling with two molecules of aldehyde (46) completes constmction of the C q carbon framework. Selective reduction of the internal triple bond of (47) is followed by dehydration and thermal isomerization to yield -carotene (21) (Fig. 10). 

This reaction was also extended to other aromatic aldehydes for the preparation of a,P unsaturated carboxyUc acids. Several mechanisms of the reaction have been proposed (45). The most accepted mechanism iavolves the reaction of the aldehyde with the enol form of the acid anhydride which is promoted by the presence of the sodium salt or of another base. The resulting reaction product is then dehydrated iato an unsaturated carboxyUc acid. 

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